HIV-1 Replication in the Central Nervous System Occurs in Two Distinct Cell Types
Figure 5
Macrophage-tropic HIV-1 variants in the CSF/CNS can be detected prior to the development of severe dementia.
(A) Longitudinal phylogenetic analysis of env sequences from one subject with dementia. The genetic distance scale bar indicates the number of nucleotide substitutions per site between env sequences. HIV-1 env sequences selected for phenotypic analyses are indicated with a black square, and the node of divergence for the CSF M-tropic population is indicated with a blue open circle. Bootstrap numbers ≥70 are indicated with an asterisk at the appropriate nodes, and bootstrap values are listed at critical nodes in the tree. Months from HAD diagnosis correspond to the following sample dates: 7/8/2002 (−21), 12/3/2002 (−16), 4/8/2004 (0), 5/11/2004 (1), and 6/3/2004 (2). (B) Single-cycle infection of HIV-1 Env-pseudotyped reporter viruses on CD4lowCCR5high 293-Affinofile cells. Receptor expression was measured as follows: CD4low = 1,214 receptors/cell, CD4high = 97,003 receptors/cell, CCR5high = 34,431 receptors/cell. Data are expressed as means of quadruplicate wells ± s.d., and results are representative of two independent experiments. (C) Single-cycle infection of HIV-1 Env-pseudotyped reporter viruses on primary human MDM. Data shown are means of duplicate wells ± s.d. for one donor, and were normalized to infection of the control macrophage-tropic HIV-1 Ba-L envelope.